A Trial to Evaluate the Effect of Itraconazole (ITZ), a CYP3A4 Inhibitor, on the Pharmacokinetics of Praliciguat (IW-1973) in Healthy Volunteers

An Open-label, 2-Period, Fixed-sequence, Phase 1 Study in Healthy Volunteers to Evaluate the Effect of Itraconazole, a Potent CYP3A Inhibitor, on the Pharmacokinetics of IW-1973

The primary objective of the study is to evaluate the effect of itraconazole (a potent cytochrome P450 isoenzyme [CYP]3A inhibitor) on the pharmacokinetics of IW-1973.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: IW-1973; Drug: Itraconazole

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Overland Park, Kansas, United States, 66211
      • IQVIA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subject is an ambulatory adult between 18 and 75 years old at the screening visit
• Subject is in good health and has no clinically significant findings on physical examination
• Body mass index is > 18 and < 30.0 kg/m2 at the screening visit
• Women of reproductive potential must have a negative pregnancy test at the time of check-in and must agree to use protocol-specified contraception throughout the duration of the study and for 2 months after the final dose of study drug
• Men must agree to use protocol-specified contraception and also to not donate sperm throughout the study and for 2 months after the final dose of study drug
• Other inclusion criteria per protocol

Exclusion Criteria:

• Any active or unstable clinically significant medical condition
• Use of any prescribed or non-prescribed medication
• Other exclusion criteria per protocol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Healthy Volunteers; Period 1: Single dose of IW-1973. Period 2: ITZ is dosed once daily (QD) for 17 days; a single dose of IW-1973 is administered 1 hour after the fourth ITZ QD dose.	Drug: IW-1973; Oral Tablet; Drug: Itraconazole; Oral Capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Area Under the Plasma Concentration Time Curve of IW-1973 From Time Zero Extrapolated to Infinity (AUC[0-inf])	Predose and up to 14 days post dose of IW-1973
Maximum Observed Plasma Concentration (Cmax) of IW-1973	Predose and up to 14 days post dose of IW-1973

Secondary Outcome Measures

Outcome Measure	Time Frame
Time to Cmax (Tmax) of IW-1973	Predose and up to 14 days post dose of IW-1973
Area Under the Concentration-Time Curve From Time Zero to 24 hours AUC(0-24) Postdose of IW-1973	Predose and up to 14 days post dose of IW-1973
Area Under the Concentration-Time Curve From Time Zero to Time of Last Quantifiable Concentration (AUC[0-last]) of IW-1973	Predose and up to 14 days post dose of IW-1973
Apparent Terminal Half-Life (t1/2) of IW-1973	Predose and up to 14 days post dose of IW-1973
Apparent Terminal Rate Constant (lambda[z]) of IW-1973	Predose and up to 14 days post dose of IW-1973
Apparent Total Plasma Clearance (CL/F) of IW-1973	Predose and up to 14 days post dose of IW-1973
Apparent Volume of Distribution (Vz/F) of IW-1973	Predose and up to 14 days post dose of IW-1973

Collaborators and Investigators

• Sponsor: Cyclerion Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): April 12, 2018
• Primary Completion (Actual): July 6, 2018
• Study Completion (Actual): July 6, 2018

Study Registration Dates

• First Submitted: April 9, 2018
• First Submitted That Met QC Criteria: April 13, 2018
• First Posted (Actual): April 17, 2018

Study Record Updates

• Last Update Posted (Actual): April 3, 2019
• Last Update Submitted That Met QC Criteria: April 1, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Gastrointestinal Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; 14-alpha Demethylase Inhibitors; Guanylyl Cyclase C Agonists; Enzyme Activators; Itraconazole; Praliciguat
• Other Study ID Numbers: C1973-104

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No